[Impact of PD-L1 status on the long-term outcomes of radical treatment of patients with prostate cancer].

A wide range of variables are associated with poor long-term outcomes of radical treatment in patients with prostate cancer (PCa). Expression of the programmed death-1 ligand 1 (PD-L1) in tumor might be a potential novel marker for PCa. AIM: to evaluate the influence of PD-L1 expression status in tumor cells on long-term results of radical treatment in patients with PCa. MATERIALS AND METHODS: a total of 45 patients with pathologically-proven PCa who undergone radical treatment and followed at N.N. Blokhin National Medical Research Center of Oncology were retrospectively analyzed. In all cases PD-L1 expression in tumor cells was evaluated by immunohistochemical studies of paraffin block sections obtained under direct control of pathologist. Positive expression of PD-L1(+) was defined as expression level in tumor cells more or equal 1%, while hyperexpression was diagnosed when expression level L1 more or equal 5%. RESULTS: PD-L1 expression and hyperexpression in tumor cells were identified in 8 (17.8%) and 6 (13.3%) cases. Median metastasis-free survival in patients with positive PD-L1 expression was 48.918 months (95% CI 42.523-55.313) and was less than in patients with negative PD-L1 expression (68.033 months, 95% CI 48.242- 87.824, p=0.090). Cancer-specific survival in patients with negative PD-L1 expression was significantly longer compared to patients with positive expression (p=0.05) and hyperexpression (p=0.024) of PD-L1 in tumor cells. Multivariate Cox analysis confirmed independent predictive value of positive expression and hyperexpression of PD-L1 in tumor cells for metastasis-free survival (HR 3.461, 95% CI 1.171-10.228, p=0.025, and HR 3.916, 95% CI 1.129-13.591, p=0.032) and cancer-specific survival (HR 7.65, 95% CI 0.69-84.51, p=0.097, and HR 9.73, 95% CI 0.87-108.78, p=0.065). CONCLUSION: According to our study and published data, positive PD-L1 expression in tumor cells is associated with poor prognosis of PCa. Given the lack of association of PD-L1 expression in tumor cells with the routine clinical and pathological characteristics of the disease, it seems reasonable to include the status of PD-L1 expression in the current predictive nomograms for patients with PCa. The results may indicate the potential benefits of developing personalized approaches to PCa treatment, particularly with targeting a PD-L1/PD-1 signaling pathway in tumor cells.

[The functional metabolic activity of the blood neutrophils in different clinical forms of brucellosis]. / Funktsional'no-metabolicheskaia aktivnost' neitrofilov krovi pri raznykh klinicheskikh formakh brutselleza.

The characteristics of the activity of alkaline phosphatase, nonspecific esterase, myeloperoxidase, lysosomal cation proteins, lipids have been determined in the cytochemical study of neutrophils in peripheral blood samples of 127 patients with acute, chronic, primary chronic brucellosis and osteochondrosis. It is expedient to use these characteristics as additional tests for the differential diagnostics of different clinical forms of brucellosis, as well as residual brucellosis and osteochondrosis.

[Natural resistance factors in brucellosis]. / Nekotorye faktory estestvennoi rezistentnosti pri brutselleze.

A higher level of the opsono-cytophagous capacity of the blood and the quantitative content of lysosomal cationic proteins in polymorphonuclear neutrophils in the blood of Fischer rats in comparison with the corresponding characteristics in normal guinea pigs has proved to be conductive to more active elimination of the infective agent from the body of the animals after their infection with brucellosis. The indices characterizing the activity and intensity of the phagocytosis of brucellae by polymorphonuclear neutrophils of the blood in combination with the determination of the amount of cationic proteins in these cells permit the objective characterization of the level of nonspecific resistance to brucellosis.

[Taxonomic position and ecology of the causative agent of brucellosis isolated from murine rodents in regions of the northern foothills of the Greater Caucasus. II. The ecological and pathogenetic characteristics of Brucella strains isolated from murine rodents]. / Taksonomicheskoe polozhenie i ékologiia vozbuditelia brutselleza, vydeliaemogo ot myshevidnykh gryzunov v raionakh severnykh predgorii Bol'shogo Kavkaza. Soobshchenie II. Ekologicheskie i patogeneticheskie osobennosti shtammov brutsell, vydeliaemykh ot myshevidnykh gryzunov.

To establish the possibility of the circulation of brucellae among the population of myomorphous rodents, the mass survey of these rodents was carried out in the mountainous and foothill regions of the Caucasus. In the area of the northern foothills of the Caucasian Mountains 23 Brucella cultures were isolated from 2715 rodents under examination; these cultures proved to be similar to B. suis 1330 in respect to their pathogenicity and the character of pathomorphological changes induced in guinea pigs. Experiments on white mice demonstrated the possibility of brucellar contamination through sexual route and through feces.

[Cytochemical changes in the peripheral blood leukocytes of guinea pigs inoculated against plague, tularemia and anthrax]. / Tsitokhimicheskie izmeneniia v leikotsitakh perifericheskoi krovi u morskikh svinok, privitykh protiv chumy, tuliaremii i sibirskoi iazvy.

The immunization of guinea pigs with trivaccine and monovaccines against plaque, tularemia and anthrax induces a decrease in the activity of acidic phosphatase in lymphocytes, as well as a decrease in the number of lymphocytes containing this enzyme. A decrease in the activity of alkaline phosphatase and peroxidase had been found to occur in neutrophil leukocytes. Besides, neutrophil leukocytes have shown an increase in the activity of acidic phosphatase and nonspecific esterases. The study based on the evaluation of the activity of the above-mentioned enzymes in lymphocytes and neutrophils has not revealed the predominant influence exercised by any of the antigens, different in their nature and used separately or in the form of a combined preparation, on immunogenesis.

[Comparative cytoenzymatic study of infectious and vaccinal processes in experimental brucellosis]. / Sravnitel'noe tsitoénzimaticheskoe issledovanie infektsionnogo i vaktsinnogo protsessov pri éksperimental'nom brutselleze.

In experiments on 240 guinea-pigs metabolic changes were found to occur in peripheral blood cells in the process of the development of brucellosis infection and after immunization. The degree and character of the activity of lysosomal enzymes depended on the time of infection and immunity formation. In comparison with the vaccinal culture of Br. abortus 19, the virulent culture of Br. abortus 544 induced greater changes in the activity of esterase, acidic and alkaline phosphatase in neutrophils, in the activity of acidic phosphatase in lymphocytes, as well as in the number of lymphocytes containing this enzyme. The data on enzymatic activity are recommended for use as a differential test for evaluating the character of the infectious and vaccinal processes.